CD27 is a member of the tumor necrosis factor receptor superfamily. [5] It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials. [6]
CD27 is a member of the tumor necrosis factor receptor superfamily. [5] It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials. [6]
During mouse embryonic development, specific (medium) expression levels of CD27 (in addition to high cKit, [7] [8] medium Gata2, [9] [10] [8] and high CD31 [8] expression levels) define the very first adult definitive hematopoietic stem cells generated in the aorta-gonad-mesonephros region. [8] Furthermore, CD27 is expressed on both naïve and activated effector T cells as well as NK cells and activated B cells. [5] It is a type I transmembrane protein with cysteine-rich domains, but once T cells have become activated, a soluble form of CD27 can be shed. [5] [6]
The protein encoded by this gene is a member of the TNF-receptor superfamily. [11] This receptor is required for generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis. [5]
When CD27 binds CD70, a signaling cascade leads to the differentiation and clonal expansion of T cells. [11] The cascade also results in improved survival and memory of cytotoxic T cells and increased production of certain cytokines. [12] This receptor transduces signals that lead to the activation of NF-κB and MAPK8/JNK. [11] Adaptor proteins TRAF2, TRAF3, and TRAF5 have been shown to mediate the signaling process of this receptor via ubiquitination. [5] [6] CD27-binding protein (SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the apoptosis induced by this receptor. [13]
In murine γδ T cells its expression has been correlated with the secretion of IFNγ. [14]
Varlilumab is an IgG1 antibody that binds to CD27 and is an experimental cancer treatment. [6] This agonist antibody stimulates CD27 when it binds. [6] The drug is in early clinical trials and appears to stimulate T cells and increase production of cytokines such as interferon-gamma. [6] [11]
CD27 has been shown to interact with SIVA1, [15] TRAF2 [16] [17] and TRAF3. [16] [17]
Some mutations can decrease the expression of CD27. Three such mutations, C53Y, C96Y, and R107C, are located in the cysteine-rich domains of CD27. [5]
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